Two acquired bone marrow failure syndromes, aplastic anemia and myelodysplastic syndromes (MDS), have in common that one, two, or all three blood cell lineages may be dangerously low. Neutropenia results in infections, anemia in fatigue and exacerbation of heart conditions, and thrombocytopenia in bleeding. Bone marrow transplantation is the only curative treatment for myelodysplasia. Immunosuppression may lead to improvement in aplastic anemia, but bone marrow transplantation is the standard of care for younger patients and those with a good performance status. Not all patients have a suitable donor, and alternative treatment strategies have to be pursued. Anemia and thrombocytopenia are major causes for complications in both diseases. Blood and platelet transfusions are frequently necessary, but transfusions are expensive and inconvenient.
For many years, growth factors that stimulate the bone marrow to produce white blood cells, in particular neutrophils, and erythropoietin, to stimulate red blood cell production, have been in use with some effect in both aplastic anemia and MDS. More recently two medications that stimulate megakaryocytes to mature and produce platelets have been developed, so- called thrombopoietin receptor (TPOR) agonists. Several studies have now tested these TPOR agonists in patients with aplastic anemia and MDS. Interestingly TPOR is not only expressed on megakaryocytes (the platelet forming cells) but also on bone marrow stem cells that give rise to all blood lineages. This represents an interesting dilemma: the administration of TPOR agonists could enhance not only platelet formation, but also red and white blood cell production, by acting on the stem cell and on megakaryocytes. On the other hand, they could stimulate immature bone marrow cells, such as leukemic precursor cells or blasts to proliferate and worsen the disease.
Careful studies have thus been undertaken in aplastic anemia and low risk MDS to assess the drugs’ benefits and risks. Eltrombopag does not seem to stimulate leukemia blasts based on studies performed on patients’ bone marrow cells in the laboratory. A study at the NIH treating patients with severe aplastic anemia with the TPOR agonist eltrombopag has yielded promising results: 11 out of 25 patients had a response with improvement in all 3 lineages. 9 out of 11 patients became transfusion-independent for platelets. Red blood cell responses occurred in 6/11 and neutrophil responses in 9/11 patients. No increase in bone marrow blasts, fibrosis, or leukemia was observed in the patients. With these promising results, additional studies in aplastic anemia and MDS are now ongoing, testing eltrombopag in combination with other standard treatments. If benefits indeed outweigh risks, treatment with eltrombopag may greatly improve quality of life and outcomes in patients with aplastic anemia and MDS.